The aim of this research will be to study the genetic control of protein structure, primarily of serum proteins. Emphasis will be placed on completing the amino acid sequence of the beta-chain of human haptoglobin. In addition, chemical and structural studies of haptoglobin beta-chains isolated from sera of other animals will be undertaken. Chemical modification studies of human haptoglobin will probe the binding site for hemoglobin. The evolutionary mutation rate of the beta-chain will be calculated and compared with the chymotrypsin family of serine proteases. Present evidence indicated that the haptoglobin beta-chain is approximately 30% identical in primary structure to the serine proteases. Limited proteolytic cleavage of intact haptoglobin by plasmin will be investigated, in human haptoglobin as well as that of other animals, to probe hemoglobin binding by haptoglobin. Biochemical characterization of other serum proteins is also proposed namely, Gc, ceruloplasmin, alpha-antitrypsin, and retinal-transporting protein. Of particular interest will be the investigation of vitamin D binding by human serum Gc protein. Initial studies will define the subunit structures of these proteins. Structural analysis will be pursued along with chemical modification studies in an attempt to correlate structure and function. Genetic variants and polymorphisms when available will also be compared structurally to their normal counterparts in order to assess genetic variation relative to protein structure and function.